The invention relates to grafted polymers.
Synthetic approaches used to enhance biocompatibility of polymers used in medical devices include bulk and surface modification of polymers. Bulk modification is mainly achieved by modifying the chemical composition throughout the polymer. In contrast, surface modification is generally achieved by surface derivation of a polymeric article. Surface modification offers one major advantage above bulk modification in that surface modification retains the material's mechanical characteristics, which are intimately related to the chemical composition of the polymer, and selectively alters the interfacial characteristics at the polymer surface.
Polymers are synthesized by polycondensation or by addition polymerization. Grafting reactions are most commonly used methods to incorporate a plurality of structures consisting of polycondensates and polyvinyls, or their combination, into one molecule. Energy initiated grafting, such as plasma grafting, UV grafting and radiation grafting, produce substances with complex structures. To date, the grafting by chemical initiated free radical polymerization can only be used for selected vinyl monomers, such as hydroxyethyl methacrylate, having a hydroxyl group which is able to covalently bond to the main chain in order to provide the initial graft site. The resulting structures of the products are polydispersed and difficult to reproduce precisely, in terms of the chain length (i.e. the introduction of a well defined number of moieties via monomer assembly).
Polymeric delivery platforms can be used to control the rate and period of drug delivery (i.e., time-release medications) and target specific areas of the body for treatment. Different polymer platforms can be employed to fulfill the goal of controlled delivery of an active agent. The three main mechanisms by which a pharmaceutical compound can be released from a polymeric delivery platform are diffusion, degradation and swelling. It is also possible to covalently attach the pharmaceutically active compound to the polymer active functional groups. This method has the advantage of the drug being targeted to the microenvironment where the therapeutic effect of the drug is required. For example if the system is designed for delivery to a tumor environment then a pH dependent release mechanism is applicable. The covalent bond between a polymer and drug can be designed to respond to hydrolysis under acidic conditions. Localized diseases are generally treated with pharmaceuticals delivered systemically. This mode of delivery is often hindered by safety, effectiveness and efficiency issues. For example systemic delivery of chemotherapeutic agents often results in side effects. The design of targeted and localized drug delivery platforms should provide better therapeutic efficacy. The system can be designed in the form of a small implant at the site of the diseased area to provide controlled release of pharmaceuticals for a prescribed period of time. In the area of cardiovascular diseases, stenting have become an acceptable therapy/implant for treating complex and unstable coronary artery lesions. The increased neointima hyperplasia and in stent restenosis remain problematic with bare metal stent procedures. The systemic administration of drugs, have failed to resolve the problem due to concentration below therapeutic effect at the target site. Accordingly endovascular stents have become the best platforms for local drug delivery in coronary arterial lesions. The use of polymers in this area has brought unique structure activity requirements in the chemical composition design. Vascular compatibility and drug release profiles remain as some of the most important and challenging parameters in the rational design of polymers in this area. A variety of stable and biodegradable polymers, with potential for drug delivery applications is currently available in the market. It is the specific properties required for a particular application that continuously drives the development of new polymers. The ideal parameters for local drug delivery are dictated by clinical considerations and there is no single polymer that can fulfill these requirements for an array of diseases.
There exists a need for copolymer systems which can be designed to provide the necessary multiple and repeated functional groups on polymers that endow the polymers with variability in both bulk and surface properties to match the needs described above. There is also a need to achieve the synthesis of such materials in a manner that tightly controls the extent of the multiplicity in function, given the unique properties and dose dependence of the functional groups, in terms of their influence on physical properties of the materials (i.e. achieving desired surface hardness, lubricity and hydrophilicity, without compromising brittleness and swelling character), or their effect on and bioreactive properties (i.e. achieving therapeutic action on cells and tissues, without compromising toxicity or desired enzymatic interactions) for a given application. The present invention addresses these technical difficulties and offers advantages over the prior art.